This schematic illustrates the steps involved in generating the human heart pump. (Image courtesy of University of Minnesota)
In a groundbreaking new study, researchers at the University of Minnesota have 3D printed a functioning, centimeter-scale human heart pump in the lab. The discovery could have major implications for studying heart disease, according to the university.
In the past, researchers have tried to 3D print cardiomyocytes, or heart muscle cells, that were derived from pluripotent human stem cells — cells with the potential to develop into any type of cell in the body. Researchers would reprogram these stem cells to heart muscle cells and then use specialized 3D printers to print them within a three-dimensional structure called an extracellular matrix.
The problem was that scientists could never reach critical cell density for the heart muscle cells to work. The researchers in this study flipped the process and reported that it worked. Their research was published in the American Heart Association journal Circulation Research.
“At first, we tried 3D printing cardiomyocytes, and we failed, too,” said lead researcher Brenda Ogle, head of the university’s Department of Biomedical Engineering in a news release. “So with our team’s expertise in stem cell research and 3D printing, we decided to try a new approach. We optimized the specialized ink made from extracellular matrix proteins, combined the ink with human stem cells and used the ink-plus-cells to 3D print the chambered structure. The stem cells were expanded to high cell densities in the structure first, and then we differentiated them to the heart muscle cells.”
The team found that they could achieve the goal of high cell density within less than a month to allow the cells to beat together just like a human heart, according to the university.
“After years of research, we were ready to give up, and then two of my biomedical engineering Ph.D. students, Molly Kupfer and Wei-Han Lin, suggested we try printing the stem cells first,” said Ogle, who is also director of the university’s Stem Cell Institute. “We decided to give it one last try. I couldn’t believe it when we looked at the dish in the lab and saw the whole thing contracting spontaneously and synchronously and able to move fluid.”
Ogle said this is also a critical advance in heart research because this new study shows how they were able to 3D print heart muscle cells in a way that the cells could organize and work together. Because the cells were differentiating right next to each other it’s more similar to how the stem cells would grow in the body and then undergo specification to heart muscle cells.
Compared to other high-profile research in the past, Ogle said this discovery creates a structure that is like a closed sac with a fluid inlet and fluid outlet, where they can measure how a heart moves blood within the body. This makes it an invaluable tool for studying heart function, she added.
“We now have a model to track and trace what is happening at the cell and molecular level in pump structure that begins to approximate the human heart,” Ogle said. “We can introduce disease and damage into the model and then study the effects of medicines and other therapeutics.”
The 3D-printed heart muscle model is about 1.5 centimeters long and was specifically designed to fit into the abdominal cavity of a mouse for further study. You can watch a video of it here.
“All of this seems like a simple concept, but how you achieve this is quite complex,” Ogle said. “We see the potential and think that our new discovery could have a transformative effect on heart research.“
The research was primarily funded by the National Institutes of Health (National Heart Lung and Blood Institute, National Institute of Biomedical Imaging and Bioengineering, and National Institute of General Medical Science) with additional funding from the National Science Foundation Graduate Research Fellowship Project and the University of Minnesota Doctoral Dissertation Fellowship.
